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By Carol A. Kemper, MD

Risk of HIV-related Illness and Nadir CD4 Counts

Source: Miller V, et al. Ann Intern Med 1999;7:570-577.

Using surveillance data collected during a large-scale, prospective observational study (EuroSIDA), Miller and colleagues assessed the evolving risk of opportunistic infection and disease progression in patients with advanced HIV infection. Data on a total of 7333 subjects from 52 clinics across Europe who either had persistently low CD4 cell counts (< 50/mm3) or CD4 counts greater than 200/mm3 were compared. The latter group was divided into four subgroups: those with a history of a nadir CD4 cell count less than 50/mm3, between 50-99/mm3, 100-149/mm3, or greater than 150/mm3. Viral load data were not available on sufficient numbers of patients for analysis. Patients were followed until they developed an AIDS defining event or death; the data were censored once an individual’s CD4 count fell below 200 or rose above 50/mm3. The median duration of follow-up for patients with CD4 counts greater than 200/mm3 was 16 months vs. six months for those with CD4 counts less than 50/mm3.

The overall rate of disease progression was about 20 times higher for patients with CD4 counts persistently below 50/mm3 compared with those with CD4 cells who were now greater than 200/mm3. The event incidence rate was 72.9 per 100 patient-years in patients with fewer than 50 CD4 cells vs. 3.9 per 100 patient-years in patients with CD4 counts presently greater than 200/mm3.

Even for those patients who had now reached higher CD4 counts, a previously low nadir CD4 count defined a modestly increased risk of disease and death. For example, the event incidence rate for patients whose CD4 counts were now greater than 200/mm3, but which had been below 50/mm3 in the past, was 5.9 per 100 patient-years compared with 8.1 for those with nadir counts of 50-99/mm3 and 3.7 for those whose counts had never fallen below 150/mm3. Older age was also significantly associated with disease progression.

Lower nadir CD4 cell counts were also associated with more rapid disease progression, varying from as little as a medium of 2-3 months for patients with a history of CD4 cell counts less than 100/mm3 compared with 15 months for those whose CD4 count had always been greater than 150/mm3. In contrast to what we see in the United States, the most frequent illnesses, in descending order, were esophageal candidiasis (20%), Kaposi sarcoma (13%), Pneumocystis carinii pneumonia (13%), and pulmonary tuberculosis (8%). Patients who have previously had extremely low CD4 cell counts in the past remain at increased risk for opportunistic infection and disease progression, although this risk is substantially smaller than those with persistently low CD4 cell counts below 50/mm3.

VRE for the Birds?

Source: Schwalbe RS, et al. Lancet 1999;353:722.

While the emergence of vancomycin-resistant strains of enterococcus (VRE) as the result of selective pressure in hospitals is of significant concern, evidence suggests that resistant enterococci are being introduced into the human population from a number of potential sources. Animal feed is believed to be a significant factor in the transmission of resistant enterococci from animals to humans in European countries. Schwalbe and colleagues successfully isolated numerous colonies of E. faecium from a bag of chicken feed commercially prepared in the United States. All of the colonies had a similar electrophoretic pattern and were resistant to ampicillin, gentamicin, streptomycin, and vancomycin, but not quinupristine/ dalfopristine. Although the isolation of enterococcus from chicken feed is apparently not unusual, the origins of this highly resistant VRE remain uncertain but represent a clear transmission risk for humans.

Amantadine and Aspiration Pneumonia

Source: Nakagawa T, et al. Lancet 1999;353:1157.

This fascinating study from Japan assessed the frequency of pneumonia in 163 elderly stroke victims randomized to receive amantadine 100 mg daily or no intervention. Stroke victims, especially those with basal ganglia impairment, often have swallowing disorders and are at increased risk for aspiration pneumonia. Nakagawa and colleagues wondered whether amantadine, which facilitates the release of dopamine from dopaminergic nerve terminals, may improve the swallow reflex in patients with a history of cerebral infarction.

Eligible subjects were ambulatory and immunocompetent. During a follow-up period of up to three years, patients receiving amantadine were at significantly less risk for pneumonia. Only five of 83 patients (6%) receiving amantadine vs. 22 of 80 (28%) receiving no active therapy developed pneumonia (P = 0.0001). Amantadine deserves further attention in high-risk populations with selective swallowing disorders at risk for aspiration.

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